You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
Record Information
Version2.0
Creation Date2010-04-23 19:56:58 UTC
Update Date2014-12-24 20:26:22 UTC
Accession NumberT3D3688
Identification
Common NameErgocristine
ClassSmall Molecule
DescriptionErgocristine is an alkaloid of the ergoline family. Like other ergoline alkaloids, it occurs in various species of vines of the Convolvulaceae (morning glory) family and in some species of lower fungi. Ergocristine is one of 3 similar peptides referred to as ergotoxine alkaloids, the other two being ergocryptine and ergocornine. Ergotoxines prepared into their hihydroergotoxine mesylates, commonly known as ergoloid mesylates, are used in the symptomatic therapy of age-related dementia. Long term exposure to some ergoline alkaloids can cause ergotism, a disease causing convulsive and gangrenous symptoms. (6, 3)
Compound Type
  • Amide
  • Amine
  • Ether
  • Fungal Toxin
  • Mycotoxin
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
Synonyms
Synonym
12'-Hydroxy-2'-(1-methyl-ethyl)-5'-(phenylmethyl)ergotaman-3'6'18-trione
2-Hydroxy-2-[1-methylethyl]-5-[phenylmethyl]ergotaman-3,6,18-trione
Chemical FormulaC35H39N5O5
Average Molecular Mass609.715 g/mol
Monoisotopic Mass609.295 g/mol
CAS Registry Number511-08-0
IUPAC NameN-[7-benzyl-2-hydroxy-5,8-dioxo-4-(propan-2-yl)-3-oxa-6,9-diazatricyclo[7.3.0.0²,⁶]dodecan-4-yl]-6-methyl-6,11-diazatetracyclo[7.6.1.0²,⁷.0¹²,¹⁶]hexadeca-1(16),2,9,12,14-pentaene-4-carboxamide
Traditional NameN-{7-benzyl-2-hydroxy-4-isopropyl-5,8-dioxo-3-oxa-6,9-diazatricyclo[7.3.0.0²,⁶]dodecan-4-yl}-6-methyl-6,11-diazatetracyclo[7.6.1.0²,⁷.0¹²,¹⁶]hexadeca-1(16),2,9,12,14-pentaene-4-carboxamide
SMILESCC(C)C1(NC(=O)C2CN(C)C3CC4=CNC5=CC=CC(=C45)C3=C2)OC2(O)C3CCCN3C(=O)C(CC3=CC=CC=C3)N2C1=O
InChI IdentifierInChI=1S/C35H39N5O5/c1-20(2)34(37-31(41)23-16-25-24-11-7-12-26-30(24)22(18-36-26)17-27(25)38(3)19-23)33(43)40-28(15-21-9-5-4-6-10-21)32(42)39-14-8-13-29(39)35(40,44)45-34/h4-7,9-12,16,18,20,23,27-29,36,44H,8,13-15,17,19H2,1-3H3,(H,37,41)
InChI KeyInChIKey=HEFIYUQVAZFDEE-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as ergotamines, dihydroergotamines, and derivatives. These are organic compounds containing an ergotamine moiety, which is structurally characterized by a benzyl substituent attached to the piperazine ring of the ergopeptine backbone.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassErgoline and derivatives
Sub ClassLysergic acids and derivatives
Direct ParentErgotamines, dihydroergotamines, and derivatives
Alternative Parents
Substituents
  • Ergotamine
  • Hybrid peptide
  • Alpha-dipeptide
  • Lysergic acid amide
  • Indoloquinoline
  • Benzoquinoline
  • Quinoline-3-carboxamide
  • N-acyl-alpha amino acid or derivatives
  • Pyrroloquinoline
  • Quinoline
  • Alpha-amino acid or derivatives
  • 3-alkylindole
  • Indole
  • Indole or derivatives
  • Isoindole or derivatives
  • Aralkylamine
  • N-alkylpiperazine
  • Monocyclic benzene moiety
  • 1,4-diazinane
  • Benzenoid
  • Oxazolidinone
  • Piperazine
  • Pyrrole
  • Pyrrolidine
  • Heteroaromatic compound
  • Oxazolidine
  • Tertiary carboxylic acid amide
  • Carboxamide group
  • Tertiary amine
  • Amino acid or derivatives
  • Lactam
  • Tertiary aliphatic amine
  • Secondary carboxylic acid amide
  • Orthocarboxylic acid derivative
  • Carboxylic acid derivative
  • Organoheterocyclic compound
  • Alkanolamine
  • Oxacycle
  • Azacycle
  • Organooxygen compound
  • Organic nitrogen compound
  • Organopnictogen compound
  • Carbonyl group
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Amine
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.18 g/LALOGPS
logP3.6ALOGPS
logP3.71ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)9.7ChemAxon
pKa (Strongest Basic)7.78ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area118.21 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity169.05 m³·mol⁻¹ChemAxon
Polarizability64.2 ųChemAxon
Number of Rings8ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-0adi-0089000000-aeb1e8528313eebff9d2JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-05fr-0192000000-6a63208107ddccf9b39dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-0006-0013093000-1b0fea51c7fe0dedfde9JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-03di-0000039000-c69211be46cc2870d7bcJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-05fr-0390000000-e1f07783820b230966fcJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-0006-0013093000-608600897b7d5682d5f7JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-0adi-0089000000-9f03a24b346c4a0525f9JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-05fr-0390000000-c889004b1cbb17a2939bJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0012029000-9a018cf7b722914999a0JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0zfu-3092021000-0a198fcee08b7c28091dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00di-6291000000-37a1ed4ec31119a247d8JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-08fr-0029024000-98afdccc16056646ad0bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00kr-3279061000-aebfaeae22d86e744678JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0g4i-9730000000-37e2f6daf69bab611e50JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0000009000-d646e0db5d212a9b1f86JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-0084049000-93ad6ca9490700177497JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00di-0090020000-64570a453017341fe142JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0000009000-21c3927cf13f38eaf54fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-0066029000-1052a1acaceff9c662e9JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-006x-2192001000-a805021c248fab52d515JSpectraViewer
Toxicity Profile
Route of ExposureOral, dermal, inhalation, and parenteral (contaminated drugs). (5)
Mechanism of ToxicityErgoline alkaloids tend to act as a group, producing complex and variable effects of partial agonism or antagonism at adrenergic, dopaminergic, and serotonergic receptors. Variables relating to these effects are influenced by the agent, dosage, species, tissue, physiological, and endocrinological state, and experimental conditions. In particular, ergoline alkaloids have been shown to have the significant affinity towards the 5-HT1 and 5-HT2 serotonin receptors, D1 and D2 dopamine receptors, and alpha-adrenergic receptors. This can result in a number of different effects, including vasoconstriction, convulsions, and hallucinations. Ergometrine is also known to have a non-receptor specific oxytocic activity. (2, 3, 4)
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesErgocristine is an alkaloid of the ergoline family. Like other ergoline alkaloids, it occurs in various species of vines of the Convolvulaceae (morning glory) family and in some species of lower fungi. Ergocristine is one of 3 similar peptides referred to as ergotoxine alkaloids, the other two being ergocryptine and ergocornine. Ergotoxines prepared into their hihydroergotoxine mesylates, commonly known as ergoloid mesylates, are used in the symptomatic therapy of age-related dementia. (6, 3)
Minimum Risk LevelNot Available
Health EffectsIngestion of ergoline alkaloids is known to cause the disease ergotism. Ergotism occurs in two forms, gangrenous and convulsive, likely depending on the different kinds and amounts of ergoline alkaloids present. (1)
SymptomsConvulsive ergotism can cause painful seizures and spasms, diarrhea, paresthesias, itching, headaches, nausea and vomiting. Usually the gastrointestinal effects precede the central nervous system effects. As well as seizures there can be hallucinations and mental effects including mania or psychosis. Gangrenous ergotism causes dry gangrene as a result of vasoconstriction induced in the more poorly vascularized distal structures, such as the fingers and toes. Symptoms include desquamation, weak periphery pulse, loss of peripheral sensation, edema and ultimately the death and loss of affected tissues. (7)
TreatmentTreatment for ergotism consists of vasodilators, anticoagulants and low molecular weight dextrans. If necessary, a sympathetic nerve blockade may be carried out, such as brachial plexus blockade. Temporary sedation (e.g. haloperidol) will be necessary in hallucination and diazepam is used for convulsions. There is no specific antidote. (8)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID31116
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkErgocristine
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. Richard JL: Some major mycotoxins and their mycotoxicoses--an overview. Int J Food Microbiol. 2007 Oct 20;119(1-2):3-10. Epub 2007 Jul 31. [17719115 ]
  2. Mantegani S, Brambilla E, Varasi M: Ergoline derivatives: receptor affinity and selectivity. Farmaco. 1999 May 30;54(5):288-96. [10418123 ]
  3. Schiff PL: Ergot and its alkaloids. Am J Pharm Educ. 2006 Oct 15;70(5):98. [17149427 ]
  4. Kvernmo T, Hartter S, Burger E: A review of the receptor-binding and pharmacokinetic properties of dopamine agonists. Clin Ther. 2006 Aug;28(8):1065-78. [16982285 ]
  5. Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
  6. Wikipedia. Ergoline. Last Updated 2 April 2010. [Link]
  7. Wikipedia. Ergotism. Last Updated 6 April 2010. [Link]
  8. Van den Enden, E. (2004). Illustrated Lecture Notes on Tropical Medicine. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Protein heterodimerization activity
Specific Function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular Weight:
51486.005 Da
References
  1. Gornemann T, Jahnichen S, Schurad B, Latte KP, Horowski R, Tack J, Flieger M, Pertz HH: Pharmacological properties of a wide array of ergolines at functional alpha(1)-adrenoceptor subtypes. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jan;376(5):321-30. Epub 2007 Dec 8. [18066532 ]
  2. Roquebert J, Demichel P: Agonist/antagonist activity of ergocristine at alpha-adrenoceptors in the rat. Fundam Clin Pharmacol. 1987;1(1):23-33. [2822556 ]
General Function:
Protein heterodimerization activity
Specific Function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1B
Uniprot ID:
P35368
Molecular Weight:
56835.375 Da
References
  1. Gornemann T, Jahnichen S, Schurad B, Latte KP, Horowski R, Tack J, Flieger M, Pertz HH: Pharmacological properties of a wide array of ergolines at functional alpha(1)-adrenoceptor subtypes. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jan;376(5):321-30. Epub 2007 Dec 8. [18066532 ]
  2. Roquebert J, Demichel P: Agonist/antagonist activity of ergocristine at alpha-adrenoceptors in the rat. Fundam Clin Pharmacol. 1987;1(1):23-33. [2822556 ]
General Function:
Alpha1-adrenergic receptor activity
Specific Function:
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name:
ADRA1D
Uniprot ID:
P25100
Molecular Weight:
60462.205 Da
References
  1. Gornemann T, Jahnichen S, Schurad B, Latte KP, Horowski R, Tack J, Flieger M, Pertz HH: Pharmacological properties of a wide array of ergolines at functional alpha(1)-adrenoceptor subtypes. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jan;376(5):321-30. Epub 2007 Dec 8. [18066532 ]
  2. Roquebert J, Demichel P: Agonist/antagonist activity of ergocristine at alpha-adrenoceptors in the rat. Fundam Clin Pharmacol. 1987;1(1):23-33. [2822556 ]
General Function:
Thioesterase binding
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular Weight:
48956.275 Da
References
  1. Roquebert J, Demichel P: Agonist/antagonist activity of ergocristine at alpha-adrenoceptors in the rat. Fundam Clin Pharmacol. 1987;1(1):23-33. [2822556 ]
General Function:
Epinephrine binding
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol.
Gene Name:
ADRA2B
Uniprot ID:
P18089
Molecular Weight:
49565.8 Da
References
  1. Roquebert J, Demichel P: Agonist/antagonist activity of ergocristine at alpha-adrenoceptors in the rat. Fundam Clin Pharmacol. 1987;1(1):23-33. [2822556 ]
General Function:
Protein homodimerization activity
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name:
ADRA2C
Uniprot ID:
P18825
Molecular Weight:
49521.585 Da
References
  1. Roquebert J, Demichel P: Agonist/antagonist activity of ergocristine at alpha-adrenoceptors in the rat. Fundam Clin Pharmacol. 1987;1(1):23-33. [2822556 ]
General Function:
Potassium channel regulator activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name:
DRD2
Uniprot ID:
P14416
Molecular Weight:
50618.91 Da
References
  1. Rowell PP, Larson BT: Ergocryptine and other ergot alkaloids stimulate the release of [3H]dopamine from rat striatal synaptosomes. J Anim Sci. 1999 Jul;77(7):1800-6. [10438027 ]